tbuckley/cabot-search huggingface dataset:
Effect of astragalus polysaccharides (PG2) treatment of adjuvant chemotherapy-induced fatigue in premenopausal patients with breast cancer.
Authors: Kun Ming Rau, Wen-Chi Shen, Shin-Cheh Chen, Cheng-Hsu Wang, Ruey Kuen Hsieh, Chao-Ming Hung, Mengting Peng, Chien-Ting Liu, Yuehshih Chang, Wen-Ling Kuo, Hsu-Huan Chou, Kun-Yun Yeh, Tsung-Han Wu, Chun-Feng Wu, Chang Pei-Hung, Yen-Min Huang, Chi-Chang Yu, Chun-Hui Lee
Journal: Journal of Clinical Oncology (2023)

537 Background: Fatigue is one of the most common symptoms of breast cancer (BC) patients who are receiving adjuvant chemotherapy. Astragalus Polysaccharides (PG2) had been proved to relieve cancer-related fatigue in advanced BC patients. The aim of this study is to evaluate the efficacy of PG2 as a complementary treatment among stage II/III BC patients with adjuvant chemotherapy of epirubicin-cyclophosphamide(EC) regimen in reduction of chemotherapy-induced toxicity and encouraging compliance with chemotherapy. Methods: This double blind, multicenter, phase II trial randomized stage II/III BC patients who would receive adjuvant EC at least 4 cycles to either PG2 500 mg or placebo on day1, 3, 8 every 21 days as the combination. Changes in chemotherapy-related fatigue score (CRFS) was evaluated by the Brief Fatigue Inventory-Taiwanese Form and incidence of Grade 3/4 neutropenia were the primary endpoints. Results: A total of 66 eligible patients were enrolled and equally randomized to PG2 and placebo groups, 30 cases in each group completed this trial. In general, there was no significant difference in the mean change of CRFS and fatigue intensity between the groups. But the CRFS and fatigue intensity in premenopausal-PG2 group were less aggravated after 4 cycles of EC than that of postmenopausal-placebo group. Persisted significance difference in CRFSs from cycle 1 day 5 (PG2: 0.6; Placebo: 1.9, P = 0.023) to cycle 4 day 15 (PG2: -0.3; Placebo: 0.7, P = 0.002). In all population, a lower proportion of patients suffered from grade 3/4 neutropenia from cycle 1 to cycle 4 were observed in the PG2 group compared to the placebo group (78.8% vs. 87.9% in intent-to-treat population). Conclusions: PG2 combined with adjuvant EC significantly improved adjuvant EC-induced fatigue in premenopausal BC patients. PG2 assists these patients with maintaining normal daily life and job activities, also less need of family support during chemotherapy. Furthermore, patients treated with PG2 might have better compliance to complete the whole course of adjuvant chemotherapy. Clinical trial information: NCT03314805 .
The association between baseline patient characteristics and alpelisib-induced hyperglycaemia in patients with HR+, HER2-, PIK3CA-mutated metastatic breast cancer.
Authors: Eva Godina, Simona Borstnar
Journal: Journal of Clinical Oncology (2023)

e13059 Background: Alpelisib (A) is a PI3Kα-selective inhibitor and degrader which, in combination with fulvestrant, has been approved for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC). Hyperglycemia is the most commonly observed adverse event of A. A pooled analysis of X2101 AND SOLAR-1 trials showed the association between five baseline patient characteristics (age, fasting plasma glucose (FPG), glycated haemoglobin, body mass index (BMI) and blood monocyte count (BMC)) and the development of A-induced hyperglycaemia (HG). We examined the association between baseline factors and the A-induced HG grade (G) ≥2 in a real-world setting. Methods: We performed the retrospective observational study and included patients (pts) with HR+, HER2-, PIK3CA-mutated metastatic breast cancer who received A + fulvestrant between Oct 18, 2019, and Oct 13, 2022, at the Institute of Oncology Ljubljana. Electronic records were reviewed. Baseline age, FPG, glycated haemoglobin, BMI and BMC before the start of A therapy and glucose levels during treatment with A were collected. Random plasma glucose values (RPG) were used for HG grading according to CTCAE V. The chi-square test was used to determine the association between the baseline characteristics and A-induced HG G ≥2. Results: Thirty-one female pts were included in the analysis. The median follow-up was 21 months, and the median duration of A treatment was 5.4 months. The baseline pts characteristics were as follows: median age 58 years (range 33–80), median FPG 5.6 mmol/L (range 3.10–8.6), median BMI 21.7 kg/m² (range 18.7–30.4), and median BMC was 10.3% (range 5.3–16.6). Baseline glycated haemoglobin values were only known for 58.1% of patients, so we did not further analyse them. The highest HG grades during treatment with A were as follows: G0 in 14 pts (45.2%), G1 in 5 pts (16.1%), G2 in 6 pts (19.4%), G3 in 6 pts (19.4 %). The calculated cut-off values associated with A-induced HG ≥2 were: age above 65 years, FPG above 5.9 mmol/L and BMC more than 11.5. None of the BMI cut-off values was associated with HG G≥2. Association between the baseline age, FPG and BMC and A-induced HG G≥2. Conclusions: Age over 65 years, FPG more than 5.9 mmol/L and BMC more than 11.5% have a statistically significant higher probability for A-induced HG G≥2. Therefore, these patients need more frequent blood glucose measurements, lifestyle adjustments and early treatment with metformin and/or other oral glucose-lowering agents. [Table: see text]
Prevalence of <i>BRCA1 </i>and <i>BRCA2 m</i>utations in an unselected cohort of Indian women with breast cancer.
Authors: Ajay Gogia, Nithin S G, Raja Pramanik, Ritu Gupta, S.V.S. Deo, Sandeep Mathur, Dayanand Sharma, Atul Batra, Chandra Prakash Prasad, Hari Krishna Raju Sagiraju
Journal: Journal of Clinical Oncology (2023)

e13004 Background: Familial breast cancer accounts for 10-15% of breast cancer cases. The prevalence of germline pathogenic mutations in breast cancer susceptibility genes 1 and 2 ( BRCA1/2) among female breast cancer patients remained variable across studies depending on the population/settings studied. The estimate varied between 8-10% of the unselected female breast cancer population. There is a lack of data regarding the prevalence of BRCA1/2 among female breast cancer patients in India. Methods: This prospective observational study included consecutive patients with breast cancer in females, registered at All India Institute of Medical Sciences (AIIMS), New Delhi, India between the period of 1st September 2022 to 25th January 2023(5 months duration). The staging description was done as per anatomic TNM staging according to AJCC 7 th edition. Mutation testing was performed in all patients by a standard next-generation sequencing (NGS) assay covering the BRCA1/2 gene. The reflex multiplex ligation by probe amplification method was performed in all cases that were negative by NGS. For patients with detected germline mutations in BRCA1/2, post-test counseling was done, and family screening was also advised. Results: A total of 210 female patients with breast cancer were sequentially included in the study. Young breast cancer (less than 35 years of age) constituted 40 (19.04%) cases. Thirty-eight patients (18.09%) women had a positive significant family history. The median age of the cohort was 46 years (range 18-85 years). Synchronous breast cancer was present in 7 (3.3%) cases. The stage distribution was stage I, 11(5.23%); stage II, 73 (34.76%); stage III, 83 (39.52%); and stage IV, 43 (20.47) %. One hundred and ten patients (52.38%) were hormone-receptor-positive, whereas 66 (31.42%) patients were HER2/neu positive. Triple-negative breast cancer (TNBC) was found in 65 (30.95%) cases. Overall, the prevalence of germline BRCA1/2 mutations was 35/210 (16.6%), which included BRCA 1 and 2 mutations in 22 (10.47%) and 12 (5.71) cases respectively. One case had mutations in both BRCA 1 and BRCA2. Young ( &lt; 35) TNBCs (22 cases/210, 10.47%) have a high propensity for detecting pathogenic BRCA1 mutation (8/22, 36.36%). Conclusions: The prevalence of pathogenic BRCA1/2 in 16.6% of our cohort of unselected consecutive breast cancer patients. It is higher than that reported in the Western population likely due to the younger population and more proportion of triple-negative breast cancer patients in our cohort.
AIPAC-003: A randomized, double-blind, placebo-controlled phase 3 trial testing eftilagimod alpha (soluble LAG-3) in patients with HER2-neg/low metastatic breast cancer receiving paclitaxel, following an open-label dose optimization.
Authors: Nuhad K. Ibrahim, Konstantinos Papadamitriou, Francois P. Duhoux, Serafin Morales Murillo, Mafalda Oliveira, Bernard Doger de Spéville, Danny Houtsma, Aart Beeker, Julio Antonio Peguero, Omkar Marathe, Frederic Triebel
Journal: Journal of Clinical Oncology (2023)

TPS1120 Background: Eftilagimod alpha (efti), a soluble LAG-3 protein, acts as an MHC class II agonist that enhances immunity by mediating antigen presenting cell and CD8 T-cell activation. Data from a randomized, phase 2b trial of efti plus paclitaxel compared to placebo plus paclitaxel in patients (pts) with HR+ HER2– metastatic breast cancer (MBC) (AIPAC; NCT02614833) showed sustained pharmacodynamic activity that was linked to improved overall survival (OS) in the efti arm. AIPAC-003 is a randomized, double-blind, placebo-controlled phase 3 trial testing efti plus paclitaxel in HER2-neg/low MBC pts, including an initial open-label dose optimization lead-in (DOL) component to determine the optimal biological dose (OBD) of efti in this combination. Methods: Enrolment for the DOL will begin in March 2023 in max. 66 pts. Primary endpoints (EP) in the DOL include safety and tolerability of 90 mg vs 30 mg efti and defining the OBD of efti in combination with weekly paclitaxel. Determination of the OBD will be based on the totality of safety and tolerability data together with overall response rate (ORR) and pharmacodynamic marker (CD8+ T cells, absolute lymphocyte count) data. In the Phase 3 component approx. 771 pts are randomized to receive either paclitaxel + efti or paclitaxel + placebo in a double-blinded fashion. The primary EP for the proposed Phase 3 is OS. Key secondary EPs include progression free survival and ORR by RECIST 1.1, quality of life and safety. Pts will receive paclitaxel (80 mg/m 2 I.V. on D1, 8 and 15 in a 4-week cycle), followed by efti or placebo (DOL: 30 or 90 mg efti; Phase 3: OBD of efti or placebo) S.C. on D1 and 15 in a 4-week cycle for up to 12 months. Key inclusion criteria: Pts with either a) HR+ and HER2-neg/low and endocrine therapy-resistant MBC or b) TNBC not eligible for anti-PD-1-based therapy. Pts must have measurable disease, ECOG PS 0-1 and no prior chemo for metastatic disease.
State mandatory paid medical leave policies and survival among adults with cancer in the US.
Authors: Justin Michael Barnes, Fumiko Chino, Kimberly J. Johnson, Zhiyuan Zheng, Xuesong Han, Robin Yabroff, Kenton J Johnston
Journal: Journal of Clinical Oncology (2023)

1511 Background: Cancer treatment is often costly and time intensive. Paid medical leave can help employed patients with cancer more effectively manage side effects and complete recommended cancer treatments without loss of income. Since 2012, several states have introduced mandatory paid medical leave policies. We examined whether mandatory paid medical leave policies were associated with better survival among working age adults with cancer. Methods: Adults ages 18 to 64 years diagnosed with cancer 2007- 2019 were identified from the Surveillance, Epidemiology, and End Results registry program covering 12 states. The primary outcome was overall survival (OS). The exposure of interest was the presence of state mandatory paid medical leave policies. Difference-in-differences (DID) analyses with additive hazards regression models compared changes in OS from pre- to post- mandatory paid sick leave policy implementation in states with vs. without paid sick leave policies. Models adjusted for year-quarter fixed effects, state fixed effects, state Medicaid expansion status, age, race, sex, marital status, metropolitan residence status, county-level income, cancer site, cancer stage, and insurance status. Clustered standard errors by state were achieved via the cluster bootstrap. The plausibility of the common trends assumption was tested using event study analyses and was satisfied for all analyses. Primary analyses focused on data from 2007-2016, where information on month of diagnosis, county, and insurance coverage status were available (note these variables are not available for 2017-2019), though sensitivity analyses with data through 2019 without these additional variables were conducted. Results: A total of 1,491,208 adults with cancer were identified. In adjusted DID analyses, after policy implementation, 1-year OS improved from 85.0% to 86.4% in states with mandatory medical leave policies compared to 85.1% to 85.6% in states without such policies. This translates to a 0.85% improvement in 1-year OS (hazard DID: -0.0007, 95% CI = -0.0016 to -0.0001, P = .027). The largest improvement was found among the uninsured population (hazard DID: -0.0038, 95% CI = -0.0076 to -0.0011, P = .013). In sensitivity analyses with abbreviated data through 2019, results were similar (DID for 1-year OS: 1.3%; hazard DID: -0.0010, 95% CI = -0.0025, 0.0001, P = .070). Conclusions: State mandatory paid medical leave was associated with improved survival for working-age adults with newly diagnosed cancer, particularly for those who are uninsured. Policy changes that better support patients through cancer treatment may pay off with improved cancer outcomes.
Use of AI-based second harmonic generation digital pathology for predicting patient survival for triple negative breast cancer patients.
Authors: Dean Tai, Yayun Ren, Elaine Chng, Kutbuddin Akbary, Wen-Hung Kuo, Kai-Wen Sky Huang
Journal: Journal of Clinical Oncology (2023)

e12526 Background: Extracellular matrix (ECM) in the stromal region has been known to be associated with tumorigenesis and metastasis in breast cancers. About 10-20% of all breast cancers are triple-negative breast cancers (TNBC), considered to be more aggressive with poorer prognosis than other types of breast cancer. AI-based Second Harmonic Generation (SHG) digital pathology, which is a fully quantitative fibrosis assessment, has been widely used innon-alcoholic steatohepatitis (NASH) and is FDA approved primary endpoint in NASH phase 2 clinical trials. In oncology, AI-based SHG digital pathology has demonstrated its relevance in survival prognosis for hepatocellular carcinoma and renal cell carcinoma after surgical treatment, based on analysis of tumor and non-tumor tissue collagen parameters. In this study, we study its potential applications for survival prognosis of TNBC patients. Methods: 68 patients with TNBC were treated by breast-cancer excision surgery. Tumor and non-tumor tissue from excised mass was imaged by SHG microscope (Genesis200, HistoIndex Pte. Ltd., Singapore). Regular follow-up was performed for patients post-operatively. A total of 33 collagen morphology features for collagen strings were quantified, such as length/width of strings, number of long/short/thick/thin strings, from tumour and non-tumour tissues. We used these collagen parameters to build two survival prediction models (RFS-index and OS-index) to predict patient’s recurrence-free survival (RFS) and overall survival (OS) years. The models were validated using the leave-one-out method. Results: Both RFS-index and OS-index were created using 10 specific collagen parameters chosen by sequential selection methods from overall 33 collagen parameters evaluated. 9 out of 10 parameters were selected from non-tumour tissue. The RFS-index can differentiate patients with RFS≥3 years (n = 36) and RFS &lt; 3 years (p &lt; 0.001) with cut-off value of RFS-index = 0.50. The OS-index can differentiate patients with OS≥5 years (n = 42) and OS &lt; 5 years (p &lt; 0.001) with cut-off value of RFS-index = 0.55. The log-rank test showed RFS-index (p = 0.026) and OS-index (p &lt; 0.001) can be used for prediction of disease-free and overall survival based on collagen parameters. Conclusions: SHG based AI-aided quantitative assessment of ECM collagen has been shown to correlate with survival rates of TNBC patients. This is a proof of concept study applying AI based digital pathology in helping predict survival rates for TNBC patients based on tumor and non-tumor tissue ECM collagen parameters. This could help identify patients with a higher risk of recurrence of disease and lower overall survival rates. Such patients can be followed-up more carefully, and be considered for earlier treatment interventions to improve their survival outcomes.
Secondary primary malignancy risk by ER, PR, and HER-2 status in post-menopausal women with breast cancer: A population-based analysis.
Authors: Muhammad Hammad Khan, Maurish Fatima, Usman Ali Akbar, Mohammad Ebad Ur Rehman, Jawad Basit, Aleena Aman, Sobaan Taj, Fatima Ali, Sindhu Vikash, Saira Yousuf, Waseem Khaliq, Nabeel Ahmad
Journal: Journal of Clinical Oncology (2023)

1050 Background: Breast cancer is the most commonly diagnosed cancer and second leading cause of death due to cancer in women in the United States. We aimed to determine site specific incidence of SPMs in post-menopausal women with primary BC using data from the US Surveillance, Epidemiology, and End Results (SEER-17) cancer registries. Methods: We retrospectively analyzed post-menopausal women aged 45 or older with a first primary breast cancer diagnosis between 2000 and 2019, excluding those aged 45 or younger or with non-breast cancers as their first malignancy. We defined SPMs as second malignancies occurring at least 6 months after the initial breast cancer diagnosis and calculated standardized incidence ratios (SIRs) and absolute excess risk (AER) using SEER*Stat. Statistical significance was determined using p-values &lt;0.05 and a 95% CI assuming a Poisson distribution of SPM incidence. Results: Among 774,965 post-menopausal women ≥45 years old with primary breast cancer, 10.8% developed SPMs, with significantly increased risk compared to the general population (SIR=1.14, 95% CI=1.13-1.15, p&lt;0.05), particularly for solid tumors (SIR=1.16, 95% CI=1.15-1.16, p&lt;0.05) and certain malignancies including salivary gland (SIR=1.77), thyroid (SIR=1.56), endocrine system (SIR=1.56), and hematological malignancies such as ALL, ANLL, and AML (SIR&gt;1.70). Women aged 45-59 and Black women had the highest risk for all malignancies. PR receptor-positive women had higher risk for thyroid SPMs, while PR-negative women had higher risk for SPMs in female genitalia, bones and joints, and hematological malignancies. HER-positive and triple-positive (HER ER PR) women had higher risk for thyroid and hematological SPMs, while triple-negative women had higher risk for ALL, ANLL, and AML. Conclusions: This study found that 11% of post-menopausal women with primary BC develop SPMs, with thyroid cancer being the most common. Black and older women (45-59 years) had a higher risk of developing SPMs. [Table: see text]
Clinico-molecular characteristics associated with outcomes in breast cancer patients treated with CDK4/6 inhibitors: Results from the AURORA Molecular Screening Initiative.
Authors: Elisa Agostinetto, Christos Sotiriou, Michail Ignatiadis, Thayane Antoniolli Crestani, David Venet, Svitlana Tyekucheva, Alexandre Irrthum, Jose A. Seoane, Martine J. Piccart-Gebhart, David A. Cameron, Susan Knox, CRISTINA EMILIA ROTARU, Dario Romagnoli, Gabriele Zoppoli, Philippe Georges Aftimos, Mafalda Oliveira, Meredith M. Regan, Luca Malorni, Matteo Benelli, Florentine Hilbers
Journal: Journal of Clinical Oncology (2023)

1019 Background: CDK4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET) is the recommended first line standard of care for patients with estrogen receptor positive (ER+), HER2-negative (HER2-) advanced breast cancer (ABC). However, not all patients derive the same benefit from this treatment. We aimed to identify factors associated with outcome in patients treated with CDK4/6i in a real-world setting. Methods: AURORA (NCT02102165) is an international program aimed at studying ABC by performing multi-omics profiling on paired primary tumors and metastases. Here we present exploratory results from AURORA patients treated with first line CDK4/6i + ET. DNA from primary and/or metastatic lesions and germline DNA was sequenced for 411 cancer-related genes. Endocrine resistance was defined according to the 5th ABC international consensus guidelines at the start of the first line. Local histology assessment of the primary tumor was used. Progression-free survival (PFS) was calculated from the start of CDK4/6i treatment until disease progression or death (whichever occurred first). Results: We analyzed 339 patients treated with CDK4/6i + ET in the first line. PFS differed significantly among the endocrine resistance subgroups (p&lt;0.001). Both TP53 and acquired ESR1 mutations were associated with shorter PFS (hazard ratio [HR] 1.59 [95% CI 1.43-6.73], p=0.004 and 3.10 [95% CI 1.16-2.18], p=0.004 respectively). In a multivariable analysis, acquired ESR1 mutations were significantly associated with worse PFS independently of endocrine resistance status (HR 2.42 [95% CI 1.01-5.79], p=0.048). Mutations in PIK3CA were not associated with outcome (HR 0.84 [95% CI 0.63-1.13], p=0.25). No PFS difference was observed between lobular and ductal tumors (HR 1.07 [95% CI 0.66-1.75], p=0.61). Conclusions: Endocrine resistance status and TP53 and acquired ESR1 mutations were associated with shorter PFS. Factors associated with poor outcome may be used to select patients to test alternative treatment strategies in clinical trials. Clinical trial information: NCT02102165 . [Table: see text]
Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial
Authors: Neeraj Agarwal, Arun A Azad, Joan Carles, Andre P Fay, Nobuaki Matsubara, Daniel Heinrich, Cezary Szczylik, Ugo De Giorgi, Jae Young Joung, Peter C C Fong, Eric Voog, Robert J Jones, Neal D Shore, Curtis Dunshee, Stefanie Zschäbitz, Jan Oldenburg, Xun Lin, Cynthia G Healy, Nicola Di Santo, Fabian Zohren, Karim Fizazi
Journal: The Lancet (2023)